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A Pharmacokinetics Study to Assess Abiraterone Acetate Capsule and Tablet Formulations in Patients With Prostate Cancer

Phase 1
Completed
Conditions
Prostate Neoplasms
Registration Number
NCT00600535
Lead Sponsor
Cougar Biotechnology, Inc.
Brief Summary

The purpose of this study is to evaluate the pharmacokinetics (how the drug concentrations change over time) of capsule and tablet formulations of CB7630 (abiraterone acetate) taken with and without food in patients with prostate cancer.

Detailed Description

This is an open-label study (identity of assigned study drug will be known) to evaluate the pharmacokinetics of abiraterone acetate in patients with prostate cancer. The study will be conducted in 4 stages: Stage 1 will measure blood levels after patients take 1 daily dose of abiraterone tablet or capsule formulations with and without food; Stage 2 will measure blood levels of single daily doses of abiraterone tablet formulation taken with or without food in parallel design until disease progression (up to 12 cycles \[28 days per cycle\]); Stages 3 and 4 will evaluate the safety and antitumor effects of abiraterone tablet formulation administered with a low dose glucocorticoid in a fasted state for up to 12 months for each stage. As of Protocol Amendment 4, all patients who have completed 12 cycles of abiraterone acetate treatment and continue to receive clinical benefit from such a treatment will enter Stage 4 and receive abiraterone acetate in a fasted condition with a low-dose glucocorticoid. Patients will continue in Stage 4 for an additional 24 cycles. After patients complete the last study visit, they will be followed every 3 months for disease progression and survival for up to 3 years. Serial pharmacokinetic samples will be collected during Stages 1 and 2. Efficacy and safety will be monitored throughout the study.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
31
Inclusion Criteria
  • Men with histologically, cytologically, or biochemically confirmed adenocarcinoma of the prostate
  • On-going androgen deprivation with serum testosterone <50 ng/dL (<2.0nmol/L)
  • Serum potassium >=3.5 mmol/L
  • Eastern Cooperative Oncology Group (ECOG) Performance Status score <2 (Karnofsky Performance Status >=50%)
  • No history of adrenal insufficiency or hyperaldosteronism
  • Any acute toxicities of prior chemotherapy, radiotherapy have resolved to a NCI CTCAE (version 3.0) grade of <=1 (chemotherapy induced alopecia and grade 2 neuropathy are excluded from this consideration)
  • No radiotherapy, chemotherapy, or immunotherapy within 30 days of administration of the study drug 1 (SD1) on Day 1
  • No surgery or local prostatic intervention within 28 days of the first dose (any clinically relevant sequelae from the surgery must have resolved prior to SD1 on Day 1)
  • Agrees to protocol-defined use of effective contraception
  • Life expectancy >12 weeks
Exclusion Criteria
  • Active or uncontrolled autoimmune disease that may require corticosteroid therapy
  • Serious or uncontrolled co-existent non-malignant disease, including active and uncontrolled infection
  • Uncontrolled hypertension
  • Protocol-defined laboratory values
  • Clinically significant heart disease as evidenced by a myocardial infarction in the past 12 months, severe or unstable angina, or New York Heart Association (NYHA) Class III or IV heart disease (patients with a history of atherosclerotic vascular disease requiring coronary or peripheral artery bypass surgery may be enrolled provided the surgery occurred at least 2 years prior to enrollment and after consultation with a cardiologist to insure that the disease is stable)
  • Other malignancy within the previous 5-years other than basal cell or squamous cell carcinomas of skin with a >30% probability of recurrence within 12 months
  • History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study medication
  • Condition or situation which, in the investigator's opinion, may put the patient at significant risk, may confound the study results, or may interfere significantly with patient's participation in the study

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
Mean plasma concentrations of abirateroneStage 1 predose Day 1, Days 2-4, Days 8-11; Stage 2 Day 1 Cycles 4, 7, 10
Maximum plasma concentrations of abirateroneStage 1 predose Day 1, Days 2-4, Days 8-11; Stage 2 Day 1 Cycles 4, 7, 10
Time to reach the maximum plasma concentration of abirateroneStage 1 predose Day 1, Days 2-4, Days 8-11; Stage 2 Day 1 Cycles 4, 7, 10
Area under the plasma-concentration-time curve from time 0 to the last quantifiable concentration of abirateroneStage 1 predose Day 1, Days 2-4, Days 8-11; Stage 2 Day 1 Cycles 4, 7, 10
Area under the plasma-concentration-time curve from time 0 to infinite time of abirateroneStage 1 predose Day 1, Days 2-4, Days 8-11; Stage 2 Day 1 Cycles 4, 7, 10
Elimination half-life of abirateroneStage 1 predose Day 1, Days 2-4, Days 8-11; Stage 2 Day 1 Cycles 4, 7, 10
Steady state trough concentration of abirateroneStage 1 predose Day 1, Days 2-4, Days 8-11; Stage 2 Day 1 Cycles 4, 7, 10
Secondary Outcome Measures
NameTimeMethod
Number of participants affected by an adverse eventUp to 30 days after the last dose of study medication
Number of patients with serum prostate specific antigen (PSA) decline according to PSA Working Group criteriaScreening; Stage 1 Day 14; Stages 2-3 Day 1, Cycles 1-12; Stage 4 every 3 cycles past Cycle 12
Number of patients with circulating tumor cells isolated from peripheral blood samples defined by cell countsScreening; Stage 1 Days 1 and 8; Stage 2 Day 1 Cycless 1, 4, 7, and 10; Stage 4 every 3 cycles past Cycle 12
Number of patients with circulating tumor cells isolated from peripheral blood samples defined by molecular characterizationScreening; Stage 2 Day 1 Cycle 1
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